6P29

N-demethylindolmycin synthase (PluN2) in complex with N-demethylindolmycin

Summary for 6P29

• Entry DOI: 10.2210/pdb6p29/pdb
• Descriptor: N-demethylindolmycin synthase (PluN2), (5S)-2-amino-5-[(1R)-1-(1H-indol-3-yl)ethyl]-1,3-oxazol-4(5H)-one, TRIETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: n-demethylindolmycin synthase, biosynthetic protein
• Biological source: Pseudoalteromonas luteoviolacea strain HI1
• Total number of polymer chains: 2
• Total formula weight: 33397.14

Authors

Du, Y.L.,Higgins, M.A.,Zhao, G.,Ryan, K.S. (deposition date: 2019-05-21, release date: 2019-08-07, Last modification date: 2024-03-13)

Primary citation

Du, Y.L.,Higgins, M.A.,Zhao, G.,Ryan, K.S.
Convergent biosynthetic transformations to a bacterial specialized metabolite.
Nat.Chem.Biol., 15:1043-1048, 2019

PubMed Abstract: Microbes produce specialized metabolites to thrive in their natural habitats. However, it is rare that a given specialized metabolite is biosynthesized via pathways with distinct intermediates and enzymes. Here, we show that the core assembly mechanism of the antibiotic indolmycin in marine gram-negative Pseudoalteromonas luteoviolacea is distinct from its counterpart in terrestrial gram-positive Streptomyces species, with a molecule that is a shunt product in the Streptomyces pathway employed as a biosynthetic substrate for a novel metal-independent N-demethylindolmycin synthase in the P. luteoviolacea pathway. To provide insight into this reaction, we solved the 1.5 Å resolution structure in complex with product and identified the active site residues. Guided by our biosynthetic insights, we then engineered the Streptomyces indolmycin producer for titer improvement. This study provides a paradigm for understanding how two unique routes to a microbial specialized metabolite can emerge from convergent biosynthetic transformations.

PubMed: 31406372
DOI: 10.1038/s41589-019-0331-5

Experimental method

X-RAY DIFFRACTION (1.5 Å)